Molecular Analysis of
| Autor: | Siva Kumar Kolluri, Clay B. Marsh, Duaa Dukhlallah, Gangqing Hu, Qing Ye, Timothy D. Eubank, Martin C. Pearce, Nancy Lan Guo, Rehab Mohamed, Alexey V. Ivanov, Marieta Gencheva |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Lung Neoplasms Docetaxel lcsh:Chemistry RNA interference Carcinoma Non-Small-Cell Lung Protein Isoforms lcsh:QH301-705.5 Spectroscopy KRAB isoform zinc finger protein EMT prognosis chemoresponse proliferation CRISPR-Cas9 RNAi Zinc finger Gene knockdown General Medicine Computer Science Applications Neoplasm Proteins Gene Expression Regulation Neoplastic Survival Rate Female medicine.drug Paclitaxel Kruppel-Like Transcription Factors Biology Catalysis Article Disease-Free Survival Inorganic Chemistry Cell Line Tumor medicine Gene silencing Humans Physical and Theoretical Chemistry Lung cancer Molecular Biology Organic Chemistry Cancer medicine.disease lcsh:Biology (General) lcsh:QD1-999 Apoptosis Drug Resistance Neoplasm Cancer research |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 3752, p 3752 (2021) International Journal of Molecular Sciences; Volume 22; Issue 7; Pages: 3752 |
| ISSN: | 1422-0067 |
| Popis: | Our previous study found that zinc finger protein 71 (ZNF71) mRNA expression was associated with chemosensitivity and its protein expression was prognostic of non-small-cell lung cancer (NSCLC). The Krüppel associated box (KRAB) transcriptional repression domain is commonly present in human zinc finger proteins, which are linked to imprinting, silencing of repetitive elements, proliferation, apoptosis, and cancer. This study revealed that ZNF71 KRAB had a significantly higher expression than the ZNF71 KRAB-less isoform in NSCLC tumors (n = 197) and cell lines (n = 117). Patients with higher ZNF71 KRAB expression had a significantly worse survival outcome than patients with lower ZNF71 KRAB expression (log-rank p = 0.04; hazard ratio (HR): 1.686 [1.026, 2.771]), whereas ZNF71 overall and KRAB-less expression levels were not prognostic in the same patient cohort. ZNF71 KRAB expression was associated with epithelial-to-mesenchymal transition (EMT) in both patient tumors and cell lines. ZNF71 KRAB was overexpressed in NSCLC cell lines resistant to docetaxel and paclitaxel treatment compared to chemo-sensitive cell lines, consistent with its association with poor prognosis in patients. Therefore, ZNF71 KRAB isoform is a more effective prognostic factor than ZNF71 overall and KRAB-less expression for NSCLC. Functional analysis using CRISPR-Cas9 and RNA interference (RNAi) screening data indicated that a knockdown/knockout of ZNF71 did not significantly affect NSCLC cell proliferation in vitro. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|